Method to enhance an immune response of nucleic acid vaccination

Abstract

A composition comprising liposomes associated with a nucleic acid operatively encoding an antigenic protein and with an assistor protein, wherein the assistor protein shares at least one epitope with the antigenic protein, and wherein the nucleic acid and said assistor protein are associated with the same liposomes is described. The composition provides an improved immune response compared to mixtures of liposomes some of which are associated with the nucleic acid and some of which are associated with the assistor protein.

1. A composition for generating an immune response in a mammal,
 wherein said composition comprises liposomes that are associated with a nucleic acid and an assistor protein, wherein the nucleic acid operatively encodes an antigenic protein or portion thereof which shares at least one epitope with the assistor protein, 
 wherein the liposomes have an average diameter in the range of 100-2,000 nm, 
 wherein the nucleic acid encoding said antigenic protein and the assistor protein are associated with the same liposomes; 
 wherein the nucleic acid is entrapped in the intravesicular space of the liposomes; and 
 the assistor protein is displayed on the surface of the same liposome, 
 whereby the nucleic acid and assistor protein will be co-delivered by the liposomes to a cell. 
 
     
     
       2. The composition of  claim 1  wherein the liposomes include at least one cationically charged component such that the liposomes have an overall positive charge. 
     
     
       3. The composition of  claim 1  wherein the antigenic protein or portion encoded by the nucleic acid and assistor protein are those of an infectious agent. 
     
     
       4. The composition of  claim 3  wherein the infectious agent is a virus. 
     
     
       5. The composition of  claim 1  in which the liposomes have an average diameter in the range of 100-400 nm. 
     
     
       6. The composition of  claim 1  wherein the liposomes comprise phospholipids selected from the group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, and combinations thereof. 
     
     
       7. A method to generate an immune response in a mammal which method comprises administering to the mammal the composition of  claim 1  to elicit an immune response which comprises an antibody response specific to the antigenic protein or assistor protein or both. 
     
     
       8. The method of  claim 7  wherein the liposomes include at least one cationically charged component such that the liposomes have an overall positive charge. 
     
     
       9. The method of  claim 7  wherein said immune response is to an infectious agent. 
     
     
       10. The method of  claim 7  wherein liposomes have an average diameter in the range of 100-400 nm. 
     
     
       11. The composition of  claim 1  wherein the nucleic acid and the assistor protein are present in a weight ratio in a range of 1,000:1 to 1:1. 
     
     
       12. The composition of  claim 1  wherein the liposomes are based substantially on phospholipids. 
     
     
       13. The composition of  claim 1  wherein the liposomes lack any further cell targeting moiety other than the assistor protein. 
     
     
       14. A composition for generating an immune response in a mammal comprising liposomes associated with a nucleic acid encoding an influenza hemagglutinin (HA) antigenic protein and an influenza HA protein that shares at least one epitope with the encoded antigenic protein;
 wherein the nucleic acid and the influenza HA protein are associated with the same liposomes; 
 wherein the nucleic acid is entrapped in the intravesicular space of the liposomes; and 
 influenza HA protein in antigenic form is displayed on the surface of same liposome, and 
 wherein the liposomes have an average diameter in the range of 100-2000 nm. 
 
     
     
       15. The composition of  claim 14  wherein the liposomes include at least one cationically charged component such that the liposomes have an overall positive charge. 
     
     
       16. The composition of  claim 14  wherein the liposomes comprise phospholipids selected from the group consisting of phosphatidyl choline, phosphatidyl ethanolamine, phosphatidyl serine, and combinations thereof. 
     
     
       17. A composition for generating an immune response in a mammal, which composition comprises liposomes formed from liposome-forming materials and wherein said liposomes are associated with a nucleic acid and an assistor protein,
 wherein the nucleic acid operatively encodes an antigenic protein or portion thereof which shares at least one epitope with the assistor protein, 
 the liposomes having an average diameter in the range of 100-2,000 nm, which liposomes are not polymerized and are based substantially on phospholipids, 
 wherein the nucleic acid encoding said antigenic protein and the assistor protein are associated with the same liposomes; 
 the antigenic protein and the assistor protein are from an infectious agent; 
 the nucleic acid is entrapped in the intra vesicular space of the liposomes; 
 the assistor protein in antigenic form is displayed on the surface of the same liposome; 
 the liposomes lack any further cell targeting moiety; 
 the liposomes include at least one cationically charged component such that the liposomes have an overall positive charge; 
 the nucleic acid and the assistor protein are present in a weight ratio in the range of 1,000:1 to 1:1. 
 
     
     
       18. The composition of  claim 17  wherein said infectious agent is an infectious virus. 
     
     
       19. The composition of  claim 18  wherein the infectious virus is Hepatitis virus or influenza virus. 
     
     
       20. The composition of  claim 17  in which the liposomes have an average diameter in the range of 100-400nm.